HUS1

Chr 7

HUS1 checkpoint clamp component

Also known as: hHUS1

NCBI Gene: 3364ENSG00000136273UniProt: O60921

The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

53
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HUS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 36 VUS of 53 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.12LOEUF
pLI 0.000
Z-score 1.23
OE 0.64 (0.39–1.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.41Z-score
OE missense 1.10 (0.96–1.25)
163 obs / 148.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.39–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (0.96–1.25)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 9 / 14.0Missense obs/exp: 163 / 148.8Syn Z: 0.64

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS36
Likely Benign1
Benign1
15
Pathogenic
36
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
33
3
0
36
Likely Benign
0
1
0
0
1
Benign
0
0
0
1
1
Total03418153

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HUS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MiR-340-3p-HUS1 axis suppresses proliferation and migration in lung adenocarcinoma cells.
Ren K et al.·Life Sci
2021
Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation.
Zimmerman ES et al.·Mol Cell Biol
2004
Psoriatic skin transcript phenotype: androgen/estrogen and cortisone/cortisol imbalance with increasing DNA damage response.
Başar Kılıç Ş et al.·Mol Biol Rep
2024
SEC61G identified as a prognostic biomarker of head and neck squamous cell carcinoma.
Shi Y et al.·Eur Arch Otorhinolaryngol
2022
Evaluation of the RHINO gene for breast cancer predisposition in Finnish breast cancer families.
Heikkinen T et al.·Breast Cancer Res Treat
2014
A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein.
Foray N et al.·EMBO J
2003
Associations between polymorphisms in target, metabolism, or transport proteins of mycophenolate sodium and therapeutic or adverse effects in kidney transplant patients.
Woillard JB et al.·Pharmacogenet Genomics
2014Cohort
Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects.
Bao S et al.·Oncogene
2004
DNA damage-induced translocation of mitochondrial factor HIGD1A into the nucleus regulates homologous recombination and radio/chemo-sensitivity.
Chen B et al.·Oncogene
2022
Examining transcriptional changes to DNA replication and repair factors over uveal melanoma subtypes.
Kucherlapati M·BMC Cancer
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Energetically equivalent structural transitions in the Rad17-Rad9-Hus1-Rad1-Rhino complex underlie the sequential progression from activation through maintenance to inactivation of the ATR-dependent DNA damage response.
Fukumoto Y et al.·Nucleic Acids Res
2026🔓 Open Access
Resection of DNA double-strand breaks activates Mre11-Rad50-Nbs1- and Rad9-Hus1-Rad1-dependent mechanisms that redundantly promote ATR checkpoint activation and end processing in Xenopus egg extracts.
Tatsukawa K et al.·Nucleic Acids Res
2024🔓 Open AccessFunctional
Using Affinity Pulldown Assays to Study Protein-Protein Interactions of Human NEIL1 Glycosylase and the Checkpoint Protein RAD9-RAD1-HUS1 (9-1-1) Complex.
McDonald DT et al.·Methods Mol Biol
2023
Structural basis for molecular interactions on the eukaryotic DNA sliding clamps PCNA and RAD9-RAD1-HUS1.
Hashimoto H et al.·J Biochem
2022
DNA binding by the Rad9A subunit of the Rad9-Rad1-Hus1 complex.
Hwang BJ et al.·PLoS One
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools